rs784567

Positions:

• chr12-53500681-G-A
• chr12-53500681-G-C
• chr12-53500681-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011538725.4(MAP3K12):​c.-691C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,368 control chromosomes in the GnomAD database, including 11,792 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (11749 hom., cov: 31)
  • Exomes 𝑓: 0.43 (43 hom.)
• Consequence: MAP3K12 XM_011538725.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

Genes affected

MAP3K12 (HGNC:6851): (mitogen-activated protein kinase kinase kinase 12) This gene encodes a member of the serine/threonine protein kinase family. This kinase contains a leucine-zipper domain and is predominately expressed in neuronal cells. The phosphorylation state of this kinase in synaptic terminals was shown to be regulated by membrane depolarization via calcineurin. This kinase forms heterodimers with leucine zipper containing transcription factors, such as cAMP responsive element binding protein (CREB) and MYC, and thus may play a regulatory role in PKA or retinoic acid induced neuronal differentiation. Alternatively spliced transcript variants encoding different proteins have been described.[provided by RefSeq, Jul 2010]

ENSG00000270175 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K12	XM_011538725.4	c.-691C>T		5_prime_UTR_premature_start_codon_gain_variant	1/14		XP_011537027.1
MAP3K12	XM_011538725.4	c.-691C>T		5_prime_UTR_variant	1/14		XP_011537027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000270175	ENST00000602306.2	n.895C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52636 AN: 151844 Hom.: 11748 Cov.: 31

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.00984

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.431 AC: 175 AN: 406 Hom.: 43 Cov.: 0 AF XY: 0.439 AC XY: 144 AN XY: 328

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.346 AC: 52638 AN: 151962 Hom.: 11749 Cov.: 31 AF XY: 0.343 AC XY: 25471 AN XY: 74240

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.00986

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.387

Alfa AF: 0.449 Hom.: 15956

Bravo AF: 0.321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.3
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs784567; hg19: chr12-53894465;